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Biomedical subjects

M Reichlin

Publications and source records attributed to M Reichlin.

At least 181 records · Page 10Linked to original sources

Antibody to Ro in a population of patients with systemic lupus erythematosus: distribution, clinical and serological associations.

Anti-Ro occurs in 1/3 of systemic lupus erythematosus (SLE) patients with equal prevalence at all ages, ages at onset of SLE, and disease durations. In SLE anti-Ro is associated with xerophthalmia but not rheumatoid factor (RF). Anti ds-DNA rather than anti-Ro or RF is associated with SLE arthritis. We found a positive correlation between increased anti ds-DNA levels and the prevalence of anti-Ro in SLE patients' sera. This reinforces the thesis that anti-Ro may have considerable value as a diagnostic marker for SLE.

Adult↗

Antibodies to single-stranded DNA in patients with discoid lupus erythematosus.

Sera from 31 patients with discoid lupus erythematosus were examined for the presence of antibodies to single-stranded and native DNA. None of these sera had antibodies to native DNA. When rabbit anti-human IgM was used, 6 of 28 patients had elevated binding, whereas only 1 of 29 patients had abnormal binding when antiIgG was used. The IgM nature of this response was confirmed when we demonstrated the binding activity in heavy fractions from gel filtration. We concluded that at least one-fifth of patients with discoid lupus erythematosus have IgM antibodies to single-stranded DNA.

Antibodies↗

Specificity of rabbit antisera for peptide 81-104 of horse cytochrome c is dominated by C-terminal residues.

Sera have been prepared in rabbits against the carboxy terminal cyanogen bromide fragment of horse cytochrome c (81-104) conjugated to bovine serum albumin (BSA). The specificity of these sera has been studied by radioimmunoassay and reveals that only peptide 81-104 binds the antibody. Neither whole cytochrome c nor peptides 1-65 and 66-80 displace 125I-81-104 from specific antibody, while cold peptides 81-104 is active in this regard, as expected. Fine specificity studies with isolated heterologous peptides 81-104 from the bovine, rabbit, canine, chicken, pigeon and tuna species of cytochrome c reveal that a major antigenic determinant is influenced by sequence positions 100 and 103 while a minor antigenic determinant is influenced by residue 92. These results are exactly mirrored and supported by inhibition studies with the isolated chymotryptic fragments 98-104 and 83-97. Studies with tryptic, chymotryptic and peptic digests of horse cytochrome c reveal that these natural proteases can generate peptides with the appropriate peptide sequences to react with antibodies produced against the peptide 81-104-BSA conjugate.

Amino Acid Sequence↗

Rapid renal clearance of immunoreactive canine plasma myoglobin.

Rates and mechanisms of myoglobin removal from plasma were examined in closed-chest dogs, using disappearance patterns of immunoreactivity and radioactivity after i.v. canine myoglobin radiolabeled with 125I. Arterial immunoreactive myoglobin concentration decreased monoexponentially over a 2-decade range, with rate constants of disappearance averaging -0.080 +/- 0.014 min-1 (+/- SD) (corresponding to half-times of disappearance of 8.9 +/- 1.5 min). Renal arteriovenous difference in immunoreactive myoglobin concentration documented extraction of the parent molecule, with extraction ratios averaging 0.36 +/- 0.06. Renal venous specific activity increased a few minutes after myoglobin administration, consistent with discharge from the kidney of nonimmunoreactive radiolabeled peptides of the parent molecule. Arterial disappearance of 125I was subsequently delayed in relation to immunoreactive myoglobin. Urinary recoveries of immunoreactive parent molecule and radiolabeled constituents were limited, averaging 2.5 +/- 1.1% and 12 +/- 1.1% over a 6-hour period. Arterial rate, constants of disappearance of immunoreactive myoglobin decreased markedly with decreases in renal perfusion produced by obstruction of renal arterial inflow. We conclude that myoglobin entering the vascular space is normally cleared rapidly by renal catabolism. Seven myoglobin concentration-time patterns during acute myocardial infarction directly reflect patterns of protein entry into the vascular space after release from injured tissue.

Animals↗

Clinical and serological differences between systemic lupus erythematosus patients with antibodies to Ro versus patients with antibodies to Ro and La.

Among 55 systemic lupus erythematosus patients having antibodies to Ro and/or La, two major groups were distinguished by titration of sera in counterimmunoelectrophoresis. The first group (30 patients) had antibodies to Ro alone. This was associated with a high incidence of antibodies to DNA (77%) and serious renal disease (53%). The second group (23 patients) had antibodies to Ro and La, and this was associated with a lower incidence of antibodies to DNA (30%) and a very low incidence of nephritis (9%). In this group a phenomenon of linkage of anti- Ro and anti-La titers was observed. Additionally two patients with only anti-La were found. Neither had clinically apparent renal disease. Thus, systemic lupus erythematosus patients with anti-Ro fall into two subgroups that differ considerably in their prevalence of anti-DNA and serious renal disease.

Antigens↗

Serologic and HLA associations in subacute cutaneous lupus erythematosus, a clinical subset of lupus erythematosus.

We studied the autoimmune serologic features and histocompatibility antigen associations of 27 patients who had a widespread, nonscarring and often photosensitive form of histologically specific cutaneous lupus erythematosus. We designated this disorder as subacute cutaneous lupus erythematosus. Skin lesions from this disorder can be distinguished from scarring discoid lupus erythematosus lesions both on a morphologic and histopathologic basis. Antinuclear and anticytoplasmic antibodies (Ro or Ro and La) and circulating immune complexes were frequently present in patients with subacute cutaneous lupus erythematosus, whereas rheumatoid factor and anti-lymphocyte, anti-DNA, anti-nRNP, and anti-Sm antibodies were found less frequently. Patients having annular skin lesions represented a particularly homogeneous subgroup in which there was a striking concordance of anti-Ro antibodies and the HLA-DR3 phenotype. These studies clearly establish that the presence of these lesions can serve as a cutaneous marker for a distinct subset of patients with lupus erythematosus who share similar clinical, serologic, and genetic features.

Adult↗

Antigenic structure of sperm whale myoglobin. I. Partition of specificities between antibodies reactive with peptides and native protein.

We have resolved anti-sperm whale Mb antibodies into two distinct populations: One population is reactive only with the native molecule, and the second is reaction with both Mb and peptide fragments. CNBr cleavage of sperm whale Mb yields three peptides: peptide I (1-55), peptide II (56-131), and peptide III (132-153). Immunoadsorbent columns made with these three peptides were used to fractionate antibody to sperm whale Mb. These columns cumulatively bind 60 to 70% of the total antibody present in the four sera studied (the amount of antibody bound by each peptide was proportional to its size). The remaining 30 to 40% of antibody could only bind specifically to an immunoadsorbent column of native Mb. This result indicates that not all antigenic determinants on the native Mb molecule are represented on peptide fragments.

Animals↗

Antigenic structure of sperm whale myoglobin. II. Characterization of antibodies preferentially reactive with peptides arising in response to immunization with the native protein.

The antigenicity of peptide fragments derived from CNBr-cleaved sperm whale Mb has been tested in competitive inhibition assays. These peptides appeared to be very poor inhibitors in a reaction involving radiolabeled sperm whale Mb with antipeptide antibodies, requiring about 10(4)-fold excess of peptides to achieve the same level of inhibition as cold native Mb. However, cold peptides competed much better with radiolabeled peptides for antibody binding than the native protein. These antibodies, preferentially reactive with peptides, originated from sera of animals immunized with the native molecule. This indicates heterogeneity of the antibodies produced against Mb and suggests the presence of diverse antibody subpopulations reactive with different antigenic forms of the protein. Results presented in this paper illustrate that competitive radioimmunoassays preferentially measure antibodies to the radiolabeled species, and this phenomenon can be used to demonstrate distinct populations among antibodies isolated to a single peptide.

Animals↗

Antinuclear antibody-negative systemic lupus erythematosus. I. Anti-Ro(SSA) and anti-La(SSB) antibodies.

Anti-Ro(SSA) and anti-La(SSB) antibodies are found in approximately 25% of systemic lupus erythematosus patients. These antibodies are also detected in lupus patients who fail to demonstrate a significant antinuclear antibody (ANA) titer when mouse liver is employed as the substrate. Approximately 5% to 10% of systemic lupus patients are in this category. These ANA-negative, Ro(SSA)-positive lupus patients generally demonstrate a prominent widespread photosensitive dermatitis and are frequently initially seen and evaluated by a dermatologist.

Antibodies, Antinuclear↗

Serological findings in patients with "ANA-negative" systemic lupus erythematosus.

Serological studies were performed on sera from 66 patients with the clinical picture of systemic lupus erythematosus (SLE). These sera failed to give a positive antinuclear antibody test when tested on cryostat sections of mouse liver and thus these patients' sera appear to be ANA negative. Precipitating antibodies to the cytoplasmic antigen Ro were found in 41 cases and of the remaining 25 sera, 18 were found to have antibodies to single stranded DNA detectable by radioimmunoassay. Thus, 50 of the 66 patients exhibited serological findings which are commonly found in ANA positive SLE patients. Studies with KB cells as immunofluorescent substrate revealed that 66% of these sera were positive for nuclear staining demonstrating that at least part of the failure of these sera to stain mouse liver is due to antigenic deficiency of this substrate. The clinical picture of these patients was dominated by a severe photosensitive dermatitis but more than half of the patients had widespread multisystem disease. As a group these patients had a low frequency of nephritis and neuropsychiatric disease. Detection of these antibodies relates these patients serologically to other SLE patients and suggests that they are best perceived as part of the clinical spectrum of SLE.

Adolescent↗

Systemic lupus erythematosus and intestinal venulitis.

A 22-yr-old woman with a 7-yr history of systemic lupus erythematosus presented with anasarca and a serum albumin of 0.8 g/dl. Renal and hepatic function were near normal; the major route of protein loss appeared to be the intestine. A full-thickness section of jejunum obtained at laparotomy demonstrated a severe, diffuse vasculitis involving the venules of the submucosa and muscularis externa with infiltration of polymorphonuclear leukocytes and macrophages, and deposits of C3. There was a similar focal damage of the walls of the small vessels in the lamina propria, and deposits of C3 and fibrinogen in a thickened basement membrane of the intestinal villi. This report documents that in systemic lupus erythematosus the intestine can be affected with a vasculitis similar to that seen in the skin and can cause thickening of the basement membrane of intestinal villi. These lesions may be responsible for protein-losing enteropathy.

Adolescent↗

Heterogeneity of precipitating antibodies in polymyositis and dermatomyositis. Characterization of the Jo-1 antibody system.

Precipitating antibodies occurring in 26 "pure" polymyositis (PM) patients and 22 "pure" dermatomyositis (DM) patients were studied by double immunodiffusion using calf thymus nuclear extract and whole calf thymus extract. Seventeen of 26 (65%) PM sera and 13 of 22 (59%) DM sera showed positive reactions, and 18, 10, and 2 sera exhibited 1, 2, and 3 precipitin lines, respectively. Common specificities were established by immunodiffusion for the 11 PM and 6 DM sera with strong precipitin lines. These were classed into three groups of shared specificity and six reactions specific for individual sera. These 9 calf thymus antigens were shown to be different from the known soluble tissue antigens Sm, nuclear RNP, Ro, and La. A 600-fold purification of the most frequently appearing system designated Jo-1 was achieved and its clinical specificity for patients with PM syndromes was established.

Antibodies↗